tbuckley/cabot-search huggingface dataset:
Invasion and Secondary Site Colonization as a Function of In Vitro Primary Tumor Matrix Stiffness: Breast to Bone Metastasis
Authors: Lekha Shah, Ayşe Latif, Kaye J. Williams, Elena Mancuso, Annalisa Tirella
Journal: Advanced Healthcare Materials (2022)

Increased breast tissue stiffness is correlated with breast cancer risk and invasive cancer progression. However, its role in promoting bone metastasis, a major cause of mortality, is not yet understood. It is previously identified that the composition and stiffness of alginate-based hydrogels mimicking normal (1-2 kPa) and cancerous (6-10 kPa) breast tissue govern phenotype of breast cancer cells (including MDA-MB-231) in vitro. Here, to understand the causal effect of primary tumor stiffness on metastatic potential, a new breast-to-bone in vitro model is described. Together with alginate-gelatin hydrogels to mimic breast tissue, 3D printed biohybrid poly-caprolactone (PCL)-composite scaffolds, decellularized following bone-ECM deposition through Saos-2 engraftment, are used to mimic the bone tissue. It is reported that higher hydrogel stiffness results in the increased migration and invasion capacity of MDA-MB 231 cells. Interestingly, increased expression of osteolytic factors PTHrP and IL-6 is observed when MDA-MB-231 cells pre-conditioned in stiffer hydrogels (10 kPa, 3% w/v gelatin) colonize the bone/PCL scaffolds. The new breast-to-bone in vitro models herein described are designed with relevant tissue microenvironmental factors and could emerge as future non-animal technological platforms for monitoring metastatic processes and therapeutic efficacy.
AACR Project GENIE Biopharma Collaborative Releases Colorectal Cancer Dataset
Journal: Cancer Discovery (2022)

Abstract The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative, a group effort involving 10 pharmaceutical companies, has released a de-identified colorectal cancer dataset. This genomic and clinical information will give researchers and clinicians more data to help them understand a patient's treatment journey and how biomarkers affect the course of their disease and outcome and help speed advances against cancer.
Antiandrogen Treatment vs Active Surveillance for Patients With Prostate Cancer
Authors: Dallin Busby, Mani Menon, Ashutosh K. Tewari
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Errors in Table
Authors: Eric Bates
Journal: JAMA Cardiology (2022)

João Pedro Ferreira, MD, PhD; Faiez Zannad, MD, PhD; Javed Butler, MD, MPH; Gerasimos Filippatos, MD, PhD; Stuart J. Pocock, PhD; Martina Brueckmann, MD; Dominik Steubl, MD; Elke Schueler, MSc, Dipl-Math; Stefan D. Anker, MD, PhD; Milton Packer, MD
Molecular Characterization of Acquired Resistance to KRASG12C–EGFR Inhibition in Colorectal Cancer
Authors: Rona Yaeger, Riccardo Mezzadra, Jenna Sinopoli, Yu Bian, Michelangelo Marasco, Esther Kaplun, Yijun Gao, HuiYong Zhao, Arnaud Da Cruz Paula, Yingjie Zhu, Almudena Chaves Perez, Kalyani Chadalavada, Edison Tse, Sudhir Chowdhry, Sydney Bowker, Qing Chang, Besnik Qeriqi, Britta Weigelt, Gouri J. Nanjangud, Michael F. Berger, Hirak Der-Torossian, Kenna Anderes, Nicholas D. Socci, Jinru Shia, Gregory J. Riely, Yonina R. Murciano-Goroff, Bob T. Li, James G. Christensen, Jorge S. Reis-Filho, David B. Solit, Elisa de Stanchina, Scott W. Lowe, Neal Rosen, Sandra Misale
Journal: Cancer Discovery (2022)

With the combination of KRASG12C and EGFR inhibitors, KRAS is becoming a druggable target in colorectal cancer. However, secondary resistance limits its efficacy. Using cell lines, patient-derived xenografts, and patient samples, we detected a heterogeneous pattern of putative resistance alterations expected primarily to prevent inhibition of ERK signaling by drugs at progression. Serial analysis of patient blood samples on treatment demonstrates that most of these alterations are detected at a low frequency except for KRASG12C amplification, a recurrent resistance mechanism that rises in step with clinical progression. Upon drug withdrawal, resistant cells with KRASG12C amplification undergo oncogene-induced senescence, and progressing patients experience a rapid fall in levels of this alteration in circulating DNA. In this new state, drug resumption is ineffective as mTOR signaling is elevated. However, our work exposes a potential therapeutic vulnerability, whereby therapies that target the senescence response may overcome acquired resistance. Clinical resistance to KRASG12C-EGFR inhibition primarily prevents suppression of ERK signaling. Most resistance mechanisms are subclonal, whereas KRASG12C amplification rises over time to drive a higher portion of resistance. This recurrent resistance mechanism leads to oncogene-induced senescence upon drug withdrawal and creates a potential vulnerability to senolytic approaches. This article is highlighted in the In This Issue feature, p. 1.
Liver sinusoidal endothelial cells induce BMP6 expression in response to non–transferrin-bound iron
Authors: Edouard Charlebois, Carine Fillebeen, John Presley, Gael Cagnone, Véronique Lisi, Vincent-Philippe Lavallée, Jean-Sébastien Joyal, Kostas Pantopoulos
Journal: Blood (2022)
Peritoneal Fluid Analysis in Peritoneal Dialysis–Associated Peritonitis
Authors: Jeffrey Perl, Ziv Harel, Sharon J. Nessim
Journal: JAMA (2022)

A 62-year-old woman undergoing peritoneal dialysis (PD) presented to the clinic with severe abdominal pain and cloudy PD fluid. Seven days prior, she inadvertently broke aseptic technique when tightening a leaking connection of her PD catheter tubing. Cloudy fluid that was drained from her PD catheter was sent for laboratory analysis. What would you do next?
Multifunctional Dual Cross‐Linked Bioadhesive Patch with Low Immunogenic Response and Wet Tissues Adhesion
Authors: Yang Tang, Guidong Gong, Xianglian He, Mengyuan Dai, Mei Chen, Bo Wang, Yajie Wang, Xiaoling Wang, Junling Guo
Journal: Advanced Healthcare Materials (2022)

Abstract The development of bioadhesives is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, that is, strong adhesion, water resistance, and high biocompatibility. Here, a biocompatible and biodegradable protein‐based bioadhesive patch (PBP) with high adhesion strength and low immunogenic response is reported. PBP exists as a strong adhesion for biological surfaces, which is higher than some conventional bioadhesives (i.e., polyethylene glycol and fibrin). Robust adhesion and strength are realized through the removal of interfacial water and fast formation of multiple supramolecular interactions induced by metal ions. The PBP's high biocompatibility is evaluated and immunogenic response in vitro and in vivo is neglected. The strong adhesion on soft biological tissues qualifies the PBP as biomedical glue outperforming some commercial products for applications in hemostasis performance, accelerated wound healing, and sealing of defected organs, anticipating to be useful as a tissue adhesive and sealant.
Molecular Monitoring in Endometrial Cancer—Ready for Prime Time?
Authors: Brooke M. Grant, Trevor J. Pugh, Amit M. Oza
Journal: Clinical Cancer Research (2022)

Summary Efforts are under way to define the role of minimally invasive strategies for molecular monitoring and risk stratification in endometrial cancer. A recent publication aims to define the association between circulating tumor DNA level and disease stage in patients with newly diagnosed endometrial cancer and determine whether sequencing of longitudinal cell-free DNA samples can be used for disease monitoring and detection of progression or recurrence. These results accelerate the current knowledge of molecular follow-up in endometrial cancer. See related article by Ashley et al., p. 410
Six-Month Follow-up after a Fourth BNT162b2 Vaccine Dose
Authors: Michal Canetti, Noam Barda, Mayan Gilboa, Victoria Indenbaum, Keren Asraf, Tal Gonen, Yael Weiss-Ottolenghi, Sharon Amit, Ram Doolman, Ella Mendelson, Laurence S Freedman, Yitshak Kreiss, Yaniv Lustig, Gili Regev-Yochay
Journal: New England Journal of Medicine (2022)

Six-Month Follow-up after a Fourth BNT162b2 Vaccine DoseTo the Editor: In a prospective cohort study involving health care workers that was described previously, 1 we evaluated the humoral response and vaccine effectiveness of a fourth dose of the BNT162b2 vaccine (Pfizer-BioNTech) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during a 6-month follow-up period in which omicron (mostly BA.1 and BA.2) was the predominant variant in Israel. 2 The absence of previous SARS-CoV-2 infection was verified by SARS-CoV-2 testing and serologic follow-up testing (see Table S1 and the Supplementary Methods in the Supplementary Appendix, available with the full text of this letter at NEJM.org).The humoral response (as assessed by the measurement of IgG and neutralizing antibodies) after receipt of the fourth vaccine dose was compared with that after receipt of the second and third doses.Vaccine effectiveness was assessed by comparing infection rates among participants who had received a fourth vaccine dose during various time periods (days 7 through 35, days 36 through 102, or days 103 through 181 after receipt of the fourth dose)
Antiandrogen Treatment vs Active Surveillance for Patients With Prostate Cancer
Authors: Laurence Klotz
Journal: JAMA Oncology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Resistance Mechanisms to Anti–Epidermal Growth Factor Receptor Therapy in <i>RAS/RAF</i> Wild-Type Colorectal Cancer Vary by Regimen and Line of Therapy
Authors: Christine M. Parseghian, Ryan Sun, Melanie Woods, Stefania Napolitano, Hey Min Lee, Jumanah Alshenaifi, Jason Willis, Shakayla Nunez, Kanwal P. Raghav, Van K. Morris, John P. Shen, Madhulika Eluri, Alexey Sorokin, Preeti Kanikarla, Eduardo Vilar, Marko Rehn, Agnes Ang, Teresa Troiani, Scott Kopetz
Journal: Journal of Clinical Oncology (2022)

PURPOSE Acquired resistance to anti–epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in KRAS/NRAS/EGFR, among other MAPK-pathway members. However, this was primarily on the basis of single-agent EGFRi trials and little is known about the resistance mechanisms of EGFRi combined with effective cytotoxic chemotherapy in previously untreated patients. METHODS We analyzed paired plasma samples from patients with RAS/BRAF/EGFR wild-type metastatic CRC enrolled in three large randomized trials evaluating EGFRi in the first line in combination with chemotherapy and as a single agent in third line. The mutational signature of the alterations acquired with therapy was evaluated. CRC cell lines with resistance to cetuximab, infusional fluorouracil, leucovorin, and oxaliplatin, and SN38 were developed, and transcriptional changes profiled. RESULTS Patients whose tumors were treated with and responded to EGFRi alone were more likely to develop acquired mutations (46%) compared with those treated in combination with cytotoxic chemotherapy (9%). Furthermore, contrary to the generally accepted hypothesis of the clonal evolution of acquired resistance, we demonstrate that baseline resistant subclonal mutations rarely expanded to become clonal at progression, and most remained subclonal or disappeared. Consistent with this clinical finding, preclinical models with acquired resistance to either cetuximab or chemotherapy were cross-resistant to the alternate agents, with transcriptomic profiles consistent with epithelial-to-mesenchymal transition. By contrast, commonly acquired resistance alterations in the MAPK pathway do not affect sensitivity to cytotoxic chemotherapy. CONCLUSION These findings support a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with EGFRi, with a greater predominance of acquired MAPK mutations after single-agent EGFRi. The proposed model has implications for prospective studies evaluating EGFRi rechallenge strategies guided by acquired MAPK mutations, and highlights the need to address transcriptional mechanisms of resistance.
Lifting Universal Masking in Schools — Covid-19 Incidence among Students and Staff
Authors: Tori L. Cowger, Eleanor J. Murray, Jaylen Clarke, Mary T. Bassett, Bisola O. Ojikutu, Sarimer M. Sánchez, Natalia Linos, Kathryn T. Hall
Journal: New England Journal of Medicine (2022)

In February 2022, Massachusetts rescinded a statewide universal masking policy in public schools, and many Massachusetts school districts lifted masking requirements during the subsequent weeks. In the greater Boston area, only two school districts — the Boston and neighboring Chelsea districts — sustained masking requirements through June 2022. The staggered lifting of masking requirements provided an opportunity to examine the effect of universal masking policies on the incidence of coronavirus disease 2019 (Covid-19) in schools.
In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe’s Disease
Authors: Jennifer L. Cohen, Pranesh Chakraborty, Karen Fung-Kee-Fung, Marisa E. Schwab, Deeksha Bali, Sarah P. Young, Michael H. Gelb, Hamid Khaledi, Alicia DiBattista, Stacey Smallshaw, Felipe Moretti, Derek Wong, Catherine Lacroix, Dina El Demellawy, Kyle C. Strickland, Jane Lougheed, Anita Moon-Grady, Billie R. Lianoglou, Paul Harmatz, Priya S. Kishnani, Tippi C. MacKenzie
Journal: New England Journal of Medicine (2022)

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.
Frequency and prognostic implications of KMT2A rearrangements in children with precursor B-cell lymphoma
Authors: Rex K. H. Au-Yeung, Laura Arias Padilla, Martin Zimmermann, Sarah Reinke, Ilske Oschlies, Gabriele Escherich, Wilhelm Woessmann, Birgit Burkhardt, Wolfram Klapper
Journal: Leukemia (2022)
Pancreatic cancer survival trends in the US from 2001 to 2014: a CONCORD‐3 study
Authors: Maja Nikšić, Pamela Minicozzi, Hannah K Weir, Heather Zimmerman, Maria J Schymura, Judith R Rees, Michel P Coleman, Claudia Allemani
Journal: Cancer Communications (2022)

Abstract Background Survival from pancreatic cancer is low worldwide. In the US, the 5‐year relative survival has been slightly higher for women, whites and younger patients than for their counterparts, and differences in age and stage at diagnosis [Corrections added Nov 16, 2022, after first online publication: a new affiliation is added to Maja Nikšić] may contribute to this pattern. We aimed to examine trends in survival by race, stage, age and sex for adults (15‐99 years) diagnosed with pancreatic cancer in the US. Methods This population‐based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001‐2014, with follow‐up to December 31, 2014. We estimated age‐specific and age‐standardized net survival at 1 and 5 years. Results Overall, 12.3% of patients were blacks, and 84.2% were whites. About 9.5% of patients were diagnosed with localized disease, but 50.5% were diagnosed at an advanced stage; slightly more among blacks, mainly among men. No substantial changes were seen over time (2001‐2003, 2004‐2008, 2009‐2014). In general, 1‐year net survival was higher in whites than in blacks (26.1% vs . 22.1% during 2001‐2003, 35.1% vs . 31.4% during 2009‐2014). This difference was particularly evident among patients with localized disease (49.6% in whites vs . 44.6% in blacks during 2001‐2003, 60.1% vs . 55.3% during 2009‐2014). The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis, and it widened over time (from 24.0% vs . 21.3% during 2001‐2003 to 39.7% vs . 31.0% during 2009‐2014). The survival gap was wider among men than among women. Conclusions Gaps in 1‐ and 5‐year survival between blacks and whites were persistent throughout 2001‐2014, especially for patients diagnosed with a localized tumor, for which surgery is currently the only treatment modality with the potential for cure.
The Role of Platelet-Derived Growth Factor in Focal Segmental Glomerulosclerosis
Authors: Ting Jia, Tong Xu, Bart Smeets, Eva Miriam Buhl, Marcus Johannes Moeller, Jürgen Floege, Barbara Mara Klinkhammer, Peter Boor
Journal: Journal of the American Society of Nephrology (2022)

FSGS is the final common pathway to nephron loss in most forms of severe or progressive glomerular injury. Although podocyte injury initiates FSGS, parietal epithelial cells (PECs) are the main effectors. Because PDGF takes part in fibrotic processes, we hypothesized that the ligand PDGF-B and its receptor PDGFR- β participate in the origin and progression of FSGS.
Evaluation of physical health status beyond daily step count using a wearable activity sensor
Authors: Zheng Xu, Nicole Zahradka, Seyvonne Ip, Amir Koneshloo, Ryan T. Roemmich, Sameep Sehgal, Kristin B. Highland, Peter C. Searson
Journal: npj Digital Medicine (2022)

Physical health status defines an individual's ability to perform normal activities of daily living and is usually assessed in clinical settings by questionnaires and/or by validated tests, e.g. timed walk tests. These measurements have relatively low information content and are usually limited in frequency. Wearable sensors, such as activity monitors, enable remote measurement of parameters associated with physical activity but have not been widely explored beyond measurement of daily step count. Here we report on results from a cohort of 22 individuals with Pulmonary Arterial Hypertension (PAH) who were provided with a Fitbit activity monitor (Fitbit Charge HR®) between two clinic visits (18.4 ± 12.2 weeks). At each clinical visit, a maximum of 26 measurements were recorded (19 categorical and 7 continuous). From analysis of the minute-to-minute step rate and heart rate we derive several metrics associated with physical activity and cardiovascular function. These metrics are used to identify subgroups within the cohort and to compare to clinical parameters. Several Fitbit metrics are strongly correlated to continuous clinical parameters. Using a thresholding approach, we show that many Fitbit metrics result in statistically significant differences in clinical parameters between subgroups, including those associated with physical status, cardiovascular function, pulmonary function, as well as biomarkers from blood tests. These results highlight the fact that daily step count is only one of many metrics that can be derived from activity monitors.
Persistent Endoplasmic Reticulum Stress Stimulated by Peptide Assemblies for Sensitizing Cancer Chemotherapy
Authors: Na Song, Yanqiu Song, Binbin Hu, Xin Liu, Xiunan Yu, Hao Zhou, Jiafu Long, Zhilin Yu
Journal: Advanced Healthcare Materials (2022)

Pharmacological targeting of endoplasmic reticulum (ER) stress represents one of important methods for disease therapy, which, however, is significantly suppressed by the ER homeostatic processe. Herein, a proof-of-concept strategy is reported for persistent stimulation of ER stress via preventing ER stress adaptation by utilizing multifunctional peptide assemblies. The strategy is established via creation of peptide assemblies with ER-targeting and chaperone glucose-regulated protein 78 (GRP78)-inhibiting functions. The peptides assemblies form well-defined nanofibers that are retrieved by ER organelles in human cervical cancer cell. The underlying mechanism studies unravel that the ER-accumulated peptide assemblies simultaneously stimulate ER stress and inhibit GRP78 refolding activity and thereby promoting endogenous protein aggregation. Combining the internalized peptide assemblies with the induced protein aggregates leads to the persistent stimulation of ER stress. The persistent ER stress induced by the peptide assemblies bestows their application in sensitizing cancer chemotherapy. Both in vitro and in vivo results confirm the enhanced cytotoxicity of drug toyocamycin against HeLa cells by peptide assemblies, thus efficiently inhibiting in vivo tumor growth. The strategy reported here discloses the fundamental keys for efficient promotion of ER stress, thus providing the guidance for development of ER-targeting-assisted cancer chemotherapy in the future.
Aberrant Hypermetabolism of Nasal Leiomyoma Mimicking Malignancy on 18F-FDG PET/CT
Authors: Kazuya Takeda, Shusuke Iwamoto, Ryuji Yasumatsu
Journal: Clinical Nuclear Medicine (2022)

Leiomyomas are benign tumors that commonly arise from the uterus. They rarely occur in the nasal cavity. Leiomyomas and leiomyosarcomas are clinically similar and may be difficult to distinguish preoperatively. Although PET has been reported to be useful for evaluating uterine smooth muscle tumors, the use of PET for evaluating sinonasal leiomyoma has not yet been reported. Here, we describe the images of a patient with leiomyoma of the nasal septum in whom intense FDG uptake was noted on PET/CT.